We have measured glucose transport, glucose metabolism, lipolysis and insulin binding in Pima Indians and Caucasian subjects over a range of obesity. Glucose transport was found to be 2 times faster in adipocyte from females than males and both man and rats. We have found no significant differences between Caucasians and Pimas in the characteristics of their obesity. We have determined an apparent dissociation between insulin binding and sensitivity of glucose transport and lipolysis to insulin and insulin binding. This suggests that there may be an abnormality in the coupling mechanism between binding and action. When subjects are overfed for 2 weeks, preliminary results suggest that there is an approximately 2-fold increase in glucose transport and metabolism that appears to be independent of short term insulin action (i.e. no change in insulin binding, sensitivity of glucose transport analysis to insulin, or the fold response of transport to insulin). Lipolysis was decreased following overfeeding. Thus, adipocytes appear to adapt to overfeeding independent of insulin action. Finally in preparation for our study of the correlation between the development of insulin resistance and obesity in the Pima Indian children we have compared metabolic clearance rates with the Bergman IVGTT modeling method in adults to determine whether the Bergman method can be used to measure insulin resistance.